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Trial registered on ANZCTR


Registration number
ACTRN12622001335785
Ethics application status
Approved
Date submitted
18/08/2022
Date registered
18/10/2022
Date last updated
14/02/2024
Date data sharing statement initially provided
18/10/2022
Date results information initially provided
14/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses of EMP-01 in Healthy Adult Volunteers
Scientific title
A Phase 1 Randomized, First-in-Human, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses of EMP-01 in Healthy Adult Volunteers
Secondary ID [1] 307595 0
EMP-01-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-traumatic stress disorder (PTSD) 327077 0
Condition category
Condition code
Mental Health 324233 324233 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
EMP-01 is being developed as a potential treatment for post-traumatic stress disorder (PTSD). This Phase I study will investigate the effects of EMP-01 in healthy volunteers when administered orally.
This is a randomised, double-blind, placebo controlled ascending dose trial that consists of 4 cohorts, with each cohort comprised of 8 participants. The cohorts will enrol in sequential order depending on when participants join the study. They will enrol in either Cohort 1, 2, 3 or 4 to receive 75mg, 125mg, 175mg or 225mg of EMP-01 or placebo respectively. For each cohort, sentinel dosing will occur, whereby 2 participants (1 randomized to receive EMP-01 and 1 randomized to receive matching placebo) will be dosed and, providing no safety concerns arise, following a 24-hour observation period and review by the SMG, the remaining 6 participants will be randomized to EMP-01 or matching placebo at a ratio of 5:1.Participants in Cohorts 1, 3 and 4 will receive a single dose of EMP-01 or placebo. Participants in Cohort 2 will receive two doses of EMP-01 or placebo, one under fasting conditions and the other under fed conditions. Participants will be administered the same Investigational Product (IP) in both treatment periods. After the last participant in each cohort has dosed, all available safety data will be reviewed by the Safety Monitoring Group (SMG) to determine whether to proceed to the next cohort. SMG review will only occur for Cohort 2 after the first, fasted dose. This will be monitored through supervised dosing.
On the morning of Day 1, Investigational Product (IP) will be administered with 240 mL of water to each participant following an overnight fast of at least 8 hours. Participants will be required to fast for a minimum of 4 hours following administration of Investigational Product (IP). With the exception of water given with the dose, participants will not be allowed fluids from 1 hour prior until 2 hours after dosing. Unlimited water will be freely available at all other times. For participants in Cohort 2, on the morning of Day 9, following an overnight fast of at least 8 hours, participants will start a high-fat high-caloric meal (breakfast). This meal will derive approximately 150, 250, and 500 to 600 calories from protein, carbohydrate, and fat, respectively. The meal must be consumed within 30 minutes. Thirty minutes after starting the meal, Treatment Period 2 Investigational Product (IP) will be administered with 240 mL of water. Participants will be required to fast for a minimum of 4 hours postdose. With the exception of water given with the dose, and milk if given as part of the meal, participants will not be allowed fluids from 1 hour prior to until 2 hours after dosing. Water will be freely available at all other times.
Intervention code [1] 324059 0
Treatment: Drugs
Comparator / control treatment
Placebo-controlled trial. Matching oral capsules containing microcrystalline cellulose will be used as placebo.
Placebo will be administered with the same restrictions as EMP-01 oral capsules.
Control group
Placebo

Outcomes
Primary outcome [1] 332054 0
To assess the safety and tolerability of EMP-01 when administered as single-ascending oral doses in healthy adult participants. This will be assessed by checking the frequency and severity of Adverse events (AEs) and also by safety laboratory results.
Adverse events will be assessed by symptom focused physical and clinical examination of any autonomic responses that the participant would report from screening to End of study.
Vital signs that are assessed include blood pressure (BP), Heart rate, Respiratory rate and Temperature. BP will be assessed using a sphygmomanometer and aural temperature will be recorded. Clinical laboratory tests and safety labs will use both blood and urine samples.
Heart rate will be assessed via a vital signs monitor. Safety laboratory tests will include hematology, serum chemistry and urinalysis.

Timepoint [1] 332054 0
For Cohorts 1, 3, and 4: Day 1 pre-dose Day 1, Day 2 and Day 8 post-dose.
Cohort 2: Day 1 pre-dose, Day 1, Day 2, Day 8, Day 9 pre-dose, Day 9, Day 10 and Day 16 post first dose.

Secondary outcome [1] 412853 0
To evaluate the Pharmacokinetic (PK) characteristics of EMP-01 and its major metabolite following a single dose of 125 mg under fed and fasted conditions in healthy adult participants.
Plasma Pharmacokinetic (PK) parameters to be assessed include Tmax, Cmax, Area under the curve or AUC (AUC0-t, AUC0- 24, AUC0-30, AUC0-inf, AUC percentage extrap), Miu z or Kel, t½, CL/F, and Vz/F, dose-normalized Cmax, dosenormalized AUC0-t, dosenormalized AUC0-30, dose-normalized AUC0-inf, and metabolite to parent ratio.
Timepoint [1] 412853 0
On Day 1, plasma samples for Pharmacokinetic (PK) will be collected predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 18 hours post EMP-01/placebo administration. On Day 2, plasma samples for Pharmacokinetic (PK) will be collected at 24 and 30 hours post dose. For Cohort 2 Day 9, plasma samples will also be collected predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 18 hours post EMP-01/placebo administration. On Day 10, plasma samples for Pharmacokinetic (PK) will be collected at 24 and 30 hours post dose.
Secondary outcome [2] 412854 0
Urine PK will be determined by analyzing the concentration of MDMA and its major metabolite R-MDA. Urine PK parameters (Ae, Fe, and CLR) and metabolic ratios for EMP-01 and its metabolite will be calculated and evaluated.
Timepoint [2] 412854 0
On Day 1, a sample of urine for PK analysis will be obtained within 2 hours before IP administration and pooled urine will be collected over the intervals 0 to 4, 4 to 8, 8 to 12, and 12 to 24 hours after IP administration. On Day 2, pooled urine will be collected from 24 to 30 hours after IP administration. PK urine collection for Cohort 2 will be the same as Days 1 and 2 on Days 9 and 10 post-first dose.

Eligibility
Key inclusion criteria
Each participant must meet all the following criteria to be enrolled in this study:
1. Male or female aged between 18 and 55 years of age, inclusive, at time of consent.
2. Female participants must have a negative serum pregnancy test result at Screening (all cohorts) and Day 8 (Cohort 2 only), and a negative urine pregnancy test at admission to the CRU on Day -1 (all cohorts), are not currently breast-feeding, and meet one of the following criteria:
a. Undergone 1 of the following sterilization procedures at least 6 months before the first dosing:
i. hysteroscopic sterilization
ii. bilateral tubal ligation or bilateral salpingectomy
iii. hysterectomy
iv. bilateral oophorectomy
v. Essure sterilization; or
b. Be postmenopausal with amenorrhea for at least 1 year before the first dosing and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status;
c. Female participants of childbearing potential must use at least one of the following protocol-specified highly effective methods or effective methods of birth control AND must agree to use barrier contraception (male condom) during heterosexual intercourse, from the time of Screening until at least 90 days after EMP-01 administration.
Highly effective methods of birth control include:
i Implant contraceptive (eg, Jadelle®)
ii. Intrauterine device (IUD) containing either copper or levonorgestrel (eg, Mirena®)
iii. Male sterilization (vasectomy).
Effective methods of birth control include:
i. Injectable contraceptive (eg, Depo Provera)
ii. Oral contraceptive pill (combined hormonal contraceptive pill or progestogen-only “mini-pill”)
iii. Vaginal contraceptive ring (eg, NuvaRing®)
It is not necessary to use any other method of contraception when complete abstinence is elected. Women of childbearing potential (WOCBP) who choose complete abstinence must continue to have pregnancy tests as per protocol. The reliability of sexual abstinence needs to be evaluated by the Investigator in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant.
3. Male participants must agree to and comply with using a double barrier method of contraception or sexual abstinence, and not donate sperm, for the duration of the study (from signing of consent to EOS visit) and for 120 days after EMP-01 administration.
For participants who are exclusively in same sex relationships, contraceptive requirements do not apply. If a participant who is in a same sex relationship at the time of signing the Informed Consent Form (ICF) becomes engaged in a heterosexual relationship, they must
agree to use contraception as described.
4. Is judged to be in good health based on medical history, physical examination, vital signs measurements, and laboratory safety tests performed at the screening visit and/or before the first dose of IP.
5. Participant weighs greater than equal 45 kg and less than equal 100 kg and has a body mass index (BMI) between 18.0 and 32.0 kg/m2 , inclusive, at Screening
6. Agrees to be available for all study visits and cooperate fully with the requirements of the study protocol, including the Schedule of Assessments.
7. Participants who smoke no more than 2 cigarettes, pipes, cigars e-cigarettes or equivalent per week, including nicotine products, from 3 months prior to Screening, can be included in the study and must be willing to abstain from smoking/using nicotine products for 24 hours prior to IP administration and during the CRU confinement period(s).
8. Capable of using common software applications on a mobile device (smartphone).
9. Willing to have the psychiatric screening, dosing session, and integration session audio recorded.
10. Willing and able to provide written informed consent indicating they understand the purpose of the study, the procedures required for the study, and are willing to participate in the study.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants who meet any of the following criteria will be excluded from this study:
1. Known allergy or hypersensitivity to MDMA or any of the excipients in the formulation.
2. History of cardiovascular, cerebrovascular, or peripheral vascular disease, including but not limited to unstable angina, myocardial infarction, congestive heart failure, cardiac arrhythmia, hypertension, hypotension, bradycardia, or tachycardia.
3. Clinically significant vital signs measurements at Screening. Clinically significant screening values measured after 5 minutes of rest in a supine position include:
- Abnormal SBP (less than 80 mmHg or more than 140 mmHg)
- Abnormal diastolic blood pressure (less than 40 mmHg or greater than 90 mmHg)
- Abnormal respiratory rate (less than 10 RR or more than 22 RR).
The BP and RR may be repeated up to 2 times at the PI’s discretion for confirmation (with 2 of 3 BPs or RRs being below the threshold).
4. Past or current history of significant mental, behavioral, or neurodevelopmental disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) including, but not limited to, diagnoses of: organic, including symptomatic, mental disorders; mental and behavioral disorders due to psychoactive substance use; schizophrenia, schizotypal, and delusional disorders; mood (affective) disorders (current only); neurotic, stress-related, and somatoform disorders; or disorders of adult personality and behavior, as assessed by the MINI screen.
5. Family (first degree relative) history of psychotic disorders such as bipolar disorder, schizophrenia, or depression with psychotic features according to the DSM-V.
6. Current suicide ideation as assessed by the C-SSRS (Baseline/Screening) up to 1 month prior to Screening; participants with a lifetime history of suicidal ideation may be excluded at the discretion of the PI or designee.
7. History of more than 25 lifetime administrations of psychedelic drugs or MDMA, or last use of a psychedelic drug or MDMA within 6 months before the Screening visit.
8. History of seizures or convulsions, with the exception of pediatric febrile seizures or increased intra-cranial pressure.
9. Has an active malignancy, or history of malignancy, excluding basal or squamous cell carcinoma of the skin, within 2 years prior to Screening.
10. Has a clinically significant history or presence of ECG findings as judged by the PI or designee at Screening, including:
a. Abnormal sinus rhythm (HR less than 40 bpm or more than 100 bpm)
b. Average QT interval corrected using Fridericia’s formula (QTcF) interval duration greater than 450 msec (males) or greater than 470 msec (females)
c. Average QRS interval greater than 120 msec after being confirmed by manual over-read
d. Average PR interval greater than 220 msec.
The ECG may be repeated up to 2 times at the PI’s discretion for confirmation (with 2 of 3 ECGs being below the threshold).
11. Has clinically significant laboratory abnormalities at Screening (confirmed by repeat assessment) including:
a. Hemoglobin less than equal 130 g per L (males) or less than equal 115 g per L (females)
b. Alanine aminotransaminase (ALT) or aspartate aminotransaminase (AST) laboratory
values greater than 1.5 × upper normal limits, or bilirubin greater than 2 × upper normal limits. Participants with Gilbert’s syndrome are not excluded.
c. An estimated creatinine clearance of less than 80 mL per min as determined by the Cockcroft-Gault equation Abnormal laboratory values can be re-tested once to confirm results prior to screen failing participant.
12. History of alcohol use disorder defined as an average weekly intake greater than 21 drinks (males) or greater than 14 drinks (females), where 1 drink is equivalent to 360 mL of beer, 150 mL of wine, or 45 mL of hard liquor within 5 years prior to Screening.
13. A history of substance use disorder or dependency within 5 years prior to Screening, or a history of recreational intravenous drug use over the last 5 years (by self-declaration), or a positive toxicology screening panel (urine test including qualitative identification of
barbiturates, tetrahydrocannabinol [THC], amphetamines, methamphetamines, ecstasy [MDMA], benzodiazepines, opiates, methadone, cotinine, and cocaine), or alcohol breath test at Screening or prior to dose administration.
14. Positive serology panel (including hepatitis B surface antigen [HBsAg] and/or confirmed current hepatitis C infection [positive hepatitis C virus {HCV} antibody confirmed with reflex HCV RNA test]) and/or positive human immunodeficiency virus (HIV) antibody/p24 antigen screen.
15. Unwilling to refrain from:
- Any systemic or topical medication, including herbal supplements (vitamins and minerals are allowed) taken within 5 times the elimination half-life of the IP or within 14 days of IP administration, whichever is longer,
- Any medications, including St. John’s Wort, known to chronically alter drug absorption or elimination processes, within 30 days of IP administration, or
- Slow-release medicinal formulations considered to still be active within 14 days of IP administration, unless in the opinion of the PI and/or Sponsor, the medication will not interfere with the study procedures or compromise safety.
16. Unwilling to refrain from alcohol and caffeine from 48 hours before IP administration through discharge from Clinical Research Unit.
17. Has received treatment with another investigational drug, investigational device, or approved therapy for investigational use within 30 days or 5 half-lives (whichever is longer) prior to IP administration. Prior participation at any time in non-invasive methodology trials in which no drugs were given is acceptable.
18. Has donated blood or plasma within 30 days prior to Screening, or had a loss of whole blood of more than 500 mL within the 30 days prior to Screening, or receipt of a blood transfusion within 1 year prior to Screening.
19. Has experienced symptoms of acute illness or chronic disease within 14 days prior to Screening, or any disease or condition (medical or surgical) that, by the determination of the PI, might compromise interpretation of safety or PK data, or would place the participant at risk as a result of participation in the study.
20. Is from a vulnerable population as defined by International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline for GCP E6 (R2), including but not limited to, employees or family member of the research staff conducting the study, or of the Sponsor, or of the CRO, or the HDEC.
21. Is unable to cooperate fully with the requirements of the study protocol, including the Schedule of Assessments, or likely to be non-compliant with any study requirements.
22. Other unspecified reasons that, in the opinion of the PI or Sponsor, make the participant unsuitable for enrollment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
An unmasked delegated pharmacist will be responsible for the dispensing of study treatments, in order to maintain blinding.
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 24903 0
New Zealand
State/province [1] 24903 0
Auckland

Funding & Sponsors
Funding source category [1] 311866 0
Commercial sector/Industry
Name [1] 311866 0
EmpathBio Australia Pty. Ltd.
Country [1] 311866 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
EmpathBio Australia Pty. Ltd.
Address
Level 7, 330 Collins Street, Melbourne Victoria 3000, Australia
Country
Australia
Secondary sponsor category [1] 313340 0
None
Name [1] 313340 0
Address [1] 313340 0
Country [1] 313340 0
Other collaborator category [1] 282370 0
Commercial sector/Industry
Name [1] 282370 0
Novotech (New Zealand) Limited
Address [1] 282370 0
Level 6, 2-6 Crowhurst Street, Newmarket, Auckland, 1023, New Zealand
Country [1] 282370 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311303 0
Central Health and Disability Ethics Committees
Ethics committee address [1] 311303 0
Health and Disability Ethics Committees, Ministry of Health, 133 Molesworth Street, PO Box 5013, Wellington, 6011
Ethics committee country [1] 311303 0
New Zealand
Date submitted for ethics approval [1] 311303 0
12/07/2022
Approval date [1] 311303 0
02/08/2022
Ethics approval number [1] 311303 0
Ethics Approval Number: 2022 FULL 12982

Summary
Brief summary
Post-traumatic stress disorder (PTSD) is a serious, chronic, life-threatening psychiatric disorder. To meet the criteria for a diagnosis of PTSD, psychiatric symptoms must be debilitating and occur after experiencing a single traumatic event or repeated traumatic experiences, such as violence, accidents, sexual and/or childhood abuse, natural disasters, terrorism and war. PTSD is a serious and debilitating disorder with a lifetime prevalence of about 1 in 25 people globally.
Current treatments rarely result in full disorder remission and generally require long-term and consistent use. Therefore, there is a need to improve and expand therapeutic options for these PTSD patients. This study will provide critical data and will inform the ongoing development of EMP-01 in the treatment of PTSD.
Trial website
Trial related presentations / publications
Public notes
Negative SARS-CoV-2 test should be produced, if required, and it should be as per CRU standards.

Contacts
Principal investigator
Name 120634 0
Dr Christian Schwabe
Address 120634 0
New Zealand Clinical Research, 3 Ferncroft Street, Grafton, Auckland, 1010
Country 120634 0
New Zealand
Phone 120634 0
+64 9 373 3474
Fax 120634 0
Email 120634 0
Christian.Schwabe@nzcr.co.nz
Contact person for public queries
Name 120635 0
Dr Christian Schwabe
Address 120635 0
New Zealand Clinical Research, 3 Ferncroft Street, Grafton, Auckland, 1010
Country 120635 0
New Zealand
Phone 120635 0
+64 9 373 3474
Fax 120635 0
Email 120635 0
vortex@nzcr.co.nz
Contact person for scientific queries
Name 120636 0
Dr Christian Schwabe
Address 120636 0
New Zealand Clinical Research, 3 Ferncroft Street, Grafton, Auckland, 1010
Country 120636 0
New Zealand
Phone 120636 0
+64 9 373 3474
Fax 120636 0
Email 120636 0
vortex@nzcr.co.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided
Current supporting documents:



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.